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71.
Dulla B Wan B Franzblau SG Kapavarapu R Reiser O Iqbal J Pal M 《Bioorganic & medicinal chemistry letters》2012,22(14):4629-4635
A series of fused and functionalized pyridine derivatives were designed, synthesized and tested for their potential antitubercular properties. All these novel compounds were prepared by using multistep methods involving the construction of pyridine ring as a key synthetic step. Some of these compounds were found to be interesting when tested for their antitubercular properties in vitro and one of them appeared as an attractive and potential antitubercular agent. 相似文献
72.
Mulakayala N Kandagatla B Ismail Rapolu RK Rao P Mulakayala C Kumar CS Iqbal J Oruganti S 《Bioorganic & medicinal chemistry letters》2012,22(15):5063-5066
A convenient and practical methodology for the synthesis of 2-aryl quinazolin-4(3H)-ones by the condensation of o-aminobenzamides with aromatic aldehydes under mild conditions using catalytic InCl(3) with good yields and high selectivities. This method has been extended for the synthesis of 5-aryl pyrazolo[4,3-d]pyrimidin-7(6H)-ones which have potential applications in medicinal chemistry. Many of these compounds were evaluated for their anti-proliferative properties in vitro against four cancer cell lines and several compounds were found to be active. Further in vitro studies indicated that inhibition of sirtuins could be the possible mechanism of action of these molecules. 相似文献
73.
Srivastava AK Srivastava PK Al-Khedhairy AA Musarrat J Shukla Y 《Mutation research》2012,747(1):22-28
Allethrin (C(19)H(26)O(3)) is non-cyano-containing pyrethroid insecticide that is used extensively for controlling flies and mosquitoes. Apart from its neurotoxic effects in non-target species, allethrin is reported to be mutagenic in bacterial systems. In this study, we observed oxidative damage-mediated genotoxicity caused by allethrin in Swiss albino mice. The genotoxic potential of allethrin was evaluated using chromosome aberrations (CAs) and a micronuclei (MN) induction assay as genetic end-points. The oral intubation of allethrin (25 and 50mg/kg b.wt.) significantly induces CAs and MN in mouse bone marrow cells. The DNA-damaging potential of allethrin was estimated in mouse liver using the DNA alkaline unwinding assay (DAUA) and by measuring the levels of 8-hydroxy-2'-deoxy-guanosine (8-OH-dG). Furthermore, a dose-dependent increase in reactive oxygen species (ROS) generation and lipid peroxidation (LPO), with a concurrent decrease in superoxide dismutase (SOD) and catalase, confirm its pro-oxidant potential. The DNA-damaging potential of allethrin was found to be mediated through the modulation of p53, p21, GADD45α and MDM-2. These results confirm the genotoxic and the pro-oxidant potential of allethrin in Swiss albino mice. 相似文献
74.
Purpose
Dry eye syndrome is a multifactorial chronic disabling disease mainly caused by the functional disruptions in the lacrimal gland. The treatment involves palliation like ocular surface lubrication and rehydration. Cell therapy involving replacement of the gland is a promising alternative for providing long-term relief to patients. This study aimed to establish functionally competent lacrimal gland cultures in–vitro and explore the presence of stem cells in the native gland and the established in-vitro cultures.Methods
Fresh human lacrimal gland from patients undergoing exenteration was harvested for cultures after IRB approval. The freshly isolated cells were evaluated by flow cytometry for expression of stem cell markers ABCG2, high ALDH1 levels and c-kit. Cultures were established on Matrigel, collagen and HAM and the cultured cells evaluated for the presence of stem cell markers and differentiating markers of epithelial (E-cadherin, EpCAM), mesenchymal (Vimentin, CD90) and myofibroblastic (α-SMA, S-100) origin by flow cytometry and immunocytochemistry. The conditioned media was tested for secretory proteins (scIgA, lactoferrin, lysozyme) post carbachol (100 µM) stimulation by ELISA.Results
Native human lacrimal gland expressed ABCG2 (mean±SEM: 3.1±0.61%), high ALDH1 (3.8±1.26%) and c-kit (6.7±2.0%). Lacrimal gland cultures formed a monolayer, in order of preference on Matrigel, collagen and HAM within 15–20 days, containing a heterogeneous population of stem-like and differentiated cells. The epithelial cells formed ‘spherules’ with duct like connections, suggestive of ductal origin. The levels of scIgA (47.43 to 61.56 ng/ml), lysozyme (24.36 to 144.74 ng/ml) and lactoferrin (32.45 to 40.31 ng/ml) in the conditioned media were significantly higher than the negative controls (p<0.05 for all comparisons).Conclusion
The study reports the novel finding of establishing functionally competent human lacrimal gland cultures in-vitro. It also provides preliminary data on the presence of stem cells and duct-like cells in the fresh and in-vitro cultured human lacrimal gland. These significant findings could pave way for cell therapy in future. 相似文献75.
76.
Two hundred Single Comb White Leg-Horn spent hens at the age of 70 weeks were purchased from a commercial layer farm. The birds were shifted to the Poultry Research Station, Department of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan. High dietary zinc (3 g/kg feed/day) was used to induce molting in all the birds after one week of acclimatization. Thereafter, birds were divided in groups of 50 birds each, with the following treatments: G1 [control; crude protein (CP)16%, no other supplement], G2 (CP18%, no other supplement), G3 (CP16%, Symbiotic, 85 mg/L drinking water) and G4 (CP16%, Probiotic, 85 mg/L in drinking water). Fifteen birds were slaughtered at 5% of peak of production for each group to collect their pituitary glands. Better egg production was seen in all the supplemented groups as compared to the control. Especially an earlier post molt production recovery and delayed decline was seen in G2 as compared to all other groups. The immunohistochemistry of the pituitary gland reveals the decrease (P≤0.01) in the cell and nucleus size as well as area of somatotrophs in G2 and G4 as compared to G1. The cell and nucleus size as well as area of lactotrophs decreased (P≤0.01) in G2, G3 and G4 as compared to G1. The better and earlier post molt production in G2 highlights the potential role of protein supplementation in connection with the decreased lactotroph size and area in molted birds.Key words: immunohistochemistry, somatotroph, lactotroph, molting, protein, probiotic, layers. 相似文献
77.
78.
Atiyatul Qadeer Gulam Rabbani Nida Zaidi Ejaz Ahmad Javed M. Khan Rizwan H. Khan 《PloS one》2012,7(11)
The molten globule (MG) state of proteins is widely detected through binding with 1-anilino-8-naphthalene sulphonate (ANS), a fluorescent dye. This strategy is based upon the assumption that when in molten globule state, the exposed hydrophobic clusters of protein are readily bound by the nonpolar anilino-naphthalene moiety of ANS molecules which then produce brilliant fluorescence. In this work, we explored the acid-induced unfolding pathway of chymopapain, a cysteine proteases from Carica papaya, by monitoring the conformational changes over a pH range 1.0–7.4 by circular dichroism, intrinsic fluorescence, ANS binding, acrylamide quenching, isothermal titration calorimetry (ITC) and dynamic light scattering (DLS). The spectroscopic measurements showed that although maximum ANS fluorescence intensity was observed at pH 1.0, however protein exhibited ∼80% loss of secondary structure which does not comply with the characteristics of a typical MG-state. In contrast at pH 1.5, chymopapain retains substantial amount of secondary structure, disrupted side chain interactions, increased hydrodynamic radii and nearly 30-fold increase in ANS fluorescence with respect to the native state, indicating that MG-state exists at pH 1.5 and not at pH 1.0. ITC measurements revealed that ANS molecules bound to chymopapain via hydrophobic interaction were more at pH 1.5 than at pH 1.0. However, a large number of ANS molecules were also involved in electrostatic interaction with protein at pH 1.0 which, together with hydrophobically interacted molecules, may be responsible for maximum ANS fluorescence. We conclude that maximum ANS-fluorescence alone may not be the criteria for determining the MG of chymopapain. Hence a comprehensive structural analysis of the intermediate is essentially required. 相似文献
79.
80.
Ahmad Ali Muhammad Abdullah Masroor Ellahi Babar Khalid Javed Asif Nadeem 《Journal of genetics》2008,87(3):219-227
An investigation to understand the dynamics and biological significance of fragile site expression, and identification of
5-fluorodeoxyuridine (FUdR) induced chromosomal gaps/breaks, were carried out in an experimental flock of 45 Suffolk sheep.
The statistical comparison revealed, highly significant variation in the frequency of chromosomal fragile site expression
between control and FUdR cultures. Mean (± S.D.) values for cells with gaps and breaks, or aberrant cell count (AC), and the
number of aberrations (NoA) per animal were 2.02 ± 0.34, 2.42 ± 0.48, 13.26 ± 0.85 and 21.87 ± 1.88 (P < 0.01) in control and FUdR cultures, respectively. The comparison of age revealed nonsignificant variation between control
and FUdR cultures. The G-band analysis of fragile site data revealed gaps in 29 autosomal and two X-chromosomal bands in the
control cultures, whereas FUdR treated cultures scored 78 unstable bands in autosomes of which 56 were significantly fragile.
X-chromosomes expressed breaks and gaps in six G-negative bands and five of them (Xq13, Xq15, Xq17, Xq24 and Xq26) were significantly
fragile. The distribution comparison of autosomal fragile sites between sex groups did not reveal any significant variation.
Female X-chromosomes were significantly more fragile than the male X-chromosomes. The distribution comparison for age groups
(lambs versus adults) revealed significantly higher number of fragile bands in adults. Comparison of published data on reciprocal
translocations in sheep with the fragile-site data obtained in this study indicated that the break sites of both phenomena
were correlated. Similarities were also found between fragile sites and breakpoints of evolutionary significance in family
Bovidae. 相似文献